Type I polyketide synthases (PKSs) are programmable, multifunctional enzymes capable of possessing all of the catalytic capacity of fatty-acid synthases (FASs). However, unlike the FAS enzyme, which iteratively extends and fully reduces the β-carbonyl generated with each extension of the hydrocarbon backbone, PKS systems utilize a discreet set of enzymatic domains for each extension and reduction of the nascent chain. These sets, commonly referred to as modules, can incorporate a variety of extenders until resulting in different side chains. They also can encode between zero and three of the reducing domains associated with FASs leading to a ketone, hydroxy, double bond, or fully saturated carbon at the beta position of the growing polyketide chain (Hopwood, D. A. and D. H. Sherman. 1990. Molecular genetics of polyketides and its comparison to fatty acid biosynthesis. Annual Review of Genetics 24:37-66).
Due to their modularity, PKS systems have been extensively explored for production of “unnatural” natural products (Weissman, K. J. and P. F. Leadlay. 2005. Combinatorial biosynthesis of reduced polyketides. Nature Reviews Microbiology 3:925-936). Hundreds of these molecules have been produced, ranging from basic lactones to modified versions of well established drugs.